Involvement of SR proteins in mRNA surveillance

Zhang, Z., Krainer, A. R. (November 2004) Involvement of SR proteins in mRNA surveillance. Molecular Cell, 16 (4). pp. 597-607. ISSN 1097-2765

URL: http://www.ncbi.nlm.nih.gov/pubmed/15546619

DOI: 10.1016/j.molcel.2004.10.031

Abstract

Nonsense mutations influence several aspects of gene expression, including mRNA stability and splicing fidelity, but the mechanism by which premature termination codons (PTCs) can apparently affect splice-site selection remains elusive. We used a model human beta-globin gene with duplicated 5' splice sites (5'ss) and found that PTCs inserted between the two 5'ss do not directly influence splicing in this system. Instead, their apparent effect on 5'ss selection in vivo is an indirect result of nonsense-mediated mRNA decay (NMD), as conditions that eliminated NMD also abrogated the effect on splicing. Remarkably, we found an unexpected function of SR proteins in targeting several mRNAs with PTCs to the NMD pathway. Overexpression of various SR proteins strongly enhanced NMD, and this effect required an RS domain. Our data argue against a universal role of PTCs in regulating pre-mRNA splicing and reveal an additional function of SR proteins in eukaryotic gene expression.

Item Type:	Paper
Uncontrolled Keywords:	Animals Blotting Western COS Cells Cercopithecus aethiops Codon, Nonsense Codon Terminator Exons Gene Expression Regulation Globins genetics Hela Cells Humans Introns Nuclear Proteins genetics metabolism Point Mutation RNA Interference RNA Precursors metabolism RNA Splicing RNA Stability RNA Messenger genetics metabolism
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > SR proteins bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mRNA dynamics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > splicing factor
CSHL Authors:	Krainer, Adrian R. Zhang, Zuo
Communities:	CSHL labs > Krainer lab
Depositing User:	CSHL Librarian
Date:	19 November 2004
Date Deposited:	17 Jan 2012 14:29
Last Modified:	09 Apr 2014 16:45
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/22523

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